Lipid oxidation inducing mutagenicity

In primary rat hepatocyte cultures 100 jiM ferric nitrilotriacetate induced five oxidation products of cellular DNA derived from both purines and pyrimidines (Abalea et al. 1999). Addition of increasing concentrations of myricetin (25-50-100 iM) simultaneously with iron prevented both lipid peroxidation and accumulation of oxidation products in DNA. Moreover, as an activation of DNA repair pathways, myricetin stimulated the release of DNA oxidation bases into culture media, especially of purine-derived oxidation products. The removal of highly mutagenic oxidation products from DNA of hepatocytes might correspond to an activation of DNA excision-repair enzymes by myricetin. This was verified by RNA blot analysis of DNA polymerase P gene expression, which was induced by myricetin in a dose-dependent manner. 

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